1,720,962 research outputs found
Discovering new lncRNAs in Zebrafish: characterization of LOC100535512 in the developing and adult central nervous system
No full textUp-regulation of LINC00520 in in vitro models of Parkinson's disease: searching for a physiological role and dysregulation in neurodegeneration
No full textThe central nervous system (CNS) expresses a large number of long non-coding RNAs (lncRNAs), non-protein coding transcripts longer than 200 nucleotides, which are important for numerous physiological processes like brain development and neural functioning. Notably, their dysregulation has been demonstrated in several neurodegenerative disorders, including Parkinson's disease (PD). The hallmark of PD is the depletion of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of cytoplasmic inclusion of a-synuclein (Lewy bodies). The neurotoxic phenotype of activated microglia contributes to PD pathogenesis by worsening inflammatory processes and exposing neurons to oxidative stress. Interestingly, we identified a disrupted expression of some lncRNAs through a meta-analysis by comparing transcriptomic data of PD patients vs control brain samples. In particular, LINC00520, which had not previously been connected to PD, showed a marked up-regulation. Our aim is to validate the results of the meta-analysis and characterize its pathophysiological role in different in vitro models. We looked at LINC00520 expression in the human neuroblastoma SH-SY5Y cells, treated with 6-OHDA to elicit an oxidative stress response, and in human monocytic THP-1 cells differentiated towards microglial-like fate with PMA and activated with LPS. Then, we included the human microglia cell line HMC3 that had been exposed to 6-OHDA or Rotenone as well as IFNg-boosted by glucose to increase the NF-kB inflammatory pathway. Our results showed a significant upregulation of LINC00520 in all in vitro PD models. Moreover, preliminary results of RNAi assays suggested that LINC00520 was involved in oxidative stress-related pathways. We also identified a potential LINC00520 ortholog in zebrafish, ZFLNCG09760, whose sequencing and functional characterization are still ongoing
Transcriptomic and morphological alterations in hTNPO3 MUT-microinjected Zebrafish embryos modelling Limb Girdle Muscular Dystrophy D2 in vivo
No full textTransportin-3, encoded by the TNPO3 gene, is physiologically involved in the translocation to the nucleus of many different proteins, such as SR proteins, which are associated with RNA metabolism. Mutations in the termination codon of the TNPO3 gene have been proved to cause Limb Girdle Muscular Dystrophy D2 (LGMD D2). More specifically, a single nucleotide deletion leads to the production of a protein with a 15 amino acid extension of its C-terminal domain. This project aimed to investigate the cause of LGMD D2, utilizing an in vivo approach, focusing on the role of TNPO3 on muscle development and to identify any potential molecular pathways linked to the disorder. This procedure involved the microinjection of mRNAs encoding the mutated form of human TNPO3 in Zebrafish embryos, to follow its effects on the myogenic processes during development. The subsequent analysis revealed changes in the gene expression profiles of Myogenic Regulatory Factors (MRFs) and muscle-specific proteins. The transcriptomic alterations are reflected on a phenotypical level by an aberrant organization of muscle fibres, as demonstrated by immunofluorescence staining. The methods we employed enabled us to gain an initial understanding of the role of Transportin-3 in muscle development and the pathogenic mechanism of its mutated form underlying LGMD D2, which has yet to be determined
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Characterization of the lncRNA LINC00520 in the developing and adult central nervous system and its correlation to neurodegenerative processes
No full textUnderstanding the mechanisms underlying human brain development and its dysfunctions has always been challenging due to the involvement of complex and dynamically regulated processes. Over the last few years, long non-coding RNAs (lncRNAs) have emerged as new players in fundamental biological processes, specifically in CNS development, neuronal proliferation, differentiation, homeostasis and synaptic plasticity. Given their importance, even a slight alteration in their expression levels has been linked to a wide range of neurological disorders, including Parkinson's disease (PD). Notably, by comparing the transcriptome of brain samples from PD patients and controls, we were able to determine that the expression of several lncRNAs, previously unrelated to the disease, was altered. We focused on LINC00520, since it was one of the most significantly up-regulated. To better define its physiopathological role, we employed several human in vitro models, ranging from neuronal to microglial cell lines. More specifically, SH-SY5Y, THP-1 and
HMC3 cell lines were treated with different compounds (6-OHDA, Rotenone, LPS, IFN
glucose) to induce oxidative and inflammatory stress responses and mimic PD conditions. Additionally, we performed RNAi assays directed against LINC00520 using the same experimental settings. Upon treatments, silencing or the combination of the two, our analyses revealed fluctuations in the expression levels of specific stress-related markers depending on LINC00520 modulation. An accurate examination of genomic traits neighbouring LINC00520 led to the identification of a syntenic region on Zebrafish chromosome 17, harbouring LOC100535512 as a potential orthologue. Interestingly, gene expression studies on Zebrafish embryos and adult tissues suggest a meaningful role of the lncRNA, especially during the gastrulation period and in the adult CNS
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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